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Biomedical subjects

J W Foreman

Publications and source records attributed to J W Foreman.

At least 37 records · Page 2Linked to original sources

10-year survey of referrals to a pediatric nephrology program.

To provide a realistic picture of the patient case load of a pediatric nephrologist in a teaching hospital, we analyzed the number, the demographics, and the reasons for patient referral to our pediatric nephrology program over a 10-year period. Between January 1, 1978, and December 31, 1987, 1,523 pediatric patients were referred to the Medical College of Virginia for evaluation and treatment of renal and electrolyte disorders. The most common reason for referral was a fluid-electrolyte disorder (30%), followed by hematuria/proteinuria (22%), chronic glomerulonephropathies (10%), hypertension (5%), nephrotic syndrome (6%), end-stage renal disease (3%), urinary tract infections (5%), and acute glomerulonephritis (3%). More than 25% of the patients were under 1 year of age at initial presentation. The rest are equally distributed among the other pediatric age groups, including adolescents. Fifty-eight percent of these patients were white, and 41% were black. Males accounted for 54% of the referrals and females for 46%. Percutaneous renal biopsies were performed under ultrasound guidance on 167 patients or a rate of 17 procedures per year. Fifty-one patients, ranging in age from 0.5 to 19 years, were followed for end-stage renal disease during the 10-year study period. Glomerular disorders accounted for 61% of the end-stage renal diseases and anatomic disorders for 39%. The yearly incidence of end-stage renal diseases over this time was 9.8 patients/million children. Twenty-six (51%) of these patients received one or more kidney transplants during the study period.

Child↗

Hypophosphatemia in a pediatric patient after major hepatic resection.

Hypophosphatemia was noted in a 20-month-old infant following major hepatic resection. The hypophosphatemia appeared to be related in part to renal wasting of phosphate, although this condition was transient. Prompt recognition and treatment prevented serious sequelae of this disorder.

Female↗

Lithium-induced nephrotic syndrome.

The nephrotic syndrome is a rare, idiosyncratic adverse renal effect of lithium that can occur with therapeutic plasma lithium levels. The syndrome is usually reversed by discontinuation of lithium treatment but may require corticosteroids. Renal biopsies reveal fusion of the foot processes of renal epithelial cells, referred to as "minimal change disease." No particular variable identifies individuals at risk for developing the nephrotic syndrome while taking lithium. The authors review the eight published cases in the English-language literature and present the case of an adolescent who developed lithium-induced nephrotic syndrome.

Adolescent↗

The effects of exogenous rat growth hormone therapy on growth of uremic rats fed an 8% protein diet.

Although the mechanisms underlying the inhibitory effects of chronic renal insufficiency on growth are poorly understood, large doses of growth hormone (GH) have been used to improve growth. The present study examines the effects of rat GH and a reduced (8%) protein diet on 75% nephrectomized weanling rats by measuring changes in growth parameters, food utilization, serum albumin concentration, and muscle water content. Significantly greater improvement in growth was found in the GH-treated uremic rats compared with the uremic controls. The mean percent change in wt, length (nose to tail tip), and cranial biparietal diameter was significantly increased in the GH-treated uremic rats, compared with the uremic controls, but foot length and femur length showed only moderate improvement. Food utilization efficiency and serum albumin concentration were significantly higher in GH-treated uremic rats compared with uremic controls, achieving levels that were not different from sham-operated rats. Muscle water content was not significantly different between GH-treated uremic rats, uremic controls, and sham-operated rats. Thus, rat GH treatment administered at an early age in mild renal insufficiency significantly improved overall growth, food efficiency, and serum albumin concentrations, despite a low protein diet, suggesting that further evaluation of this form of therapy for growth failure of uremia is warranted.

Animals↗

Cystinosis.

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Cysteamine↗

Characteristics of cystine uptake by cultured LLC-PK1 cells.

The characteristics of the uptake of L-cystine by LLC-PK1 cells were examined. The uptake diminished with time in culture after passage of cells while the uptake of sugar increased. In 48-h-cultured cells at a range of cystine concentrations including physiological levels uptake occurred via a saturable process which was independent of medium sodium concentration and pH. No inhibition of cystine uptake occurred in the presence of lysine which is known to share the cystine transport system in uncultured renal proximal tubule cells and brush-border membrane vesicles. Glutamate was a potent inhibitor of cystine uptake and participated in heteroexchange diffusion with cystine. The cystine-glutamate transport process resembles that of cultured human fibroblasts. The inability of these cells to reflect the genetically determined cystine-lysine system which is altered in the kidney in human cystinuria makes them an inappropriate model of the renal tubule cell cystine transport system. On the other hand, they may provide a model system for examining the factors which determine the presence of the various cystine transport process.

Amino Acids↗

Chronic renal failure in infants and children.

Chronic renal failure is an uncommon problem for pediatricians, but early recognition is important for maximizing growth and minimizing complications. Marked strides have been made in understanding and treating renal osteodystrophy. Recombinant erythropoietin holds the promise of reversing the anemia associated with renal insufficiency. Dialysis remains an important therapy for sustaining these children, and transplantation offers realistic hope for a functioning kidney.

Aluminum↗

Characteristics of lysine transport by isolated rat renal cortical tubule fragments.

The uptake of L-lysine was examined in isolated renal cortical tubules. Lysine was actively taken up by the renal tubule cells isolated from 7-week-old rats. No metabolism of the transported lysine was found. There was no evidence for sodium-dependence of lysine uptake. Concentration dependence studies revealed that the lysine was taken up by one saturable transport system with a Km of 1.66 mmol/l and Vmax of 7 mmol/l intracellular fluid per 10 min. Lysine also entered by a non-saturable pathway. Arginine and ornithine inhibited the initial uptake of lysine. Cystine increased the efflux of lysine from preloaded renal cells via hetero-exchange, indicating that a common system exists for these two amino acids.

Animals↗

Effect of cystine dimethylester on renal solute handling and isolated renal tubule transport in the rat: a new model of the Fanconi syndrome.

The effect of cystine dimethylester on the renal handling of phosphate, glucose, alpha-amino nitrogen, amino acids, and protein in vivo and on the uptake of lysine, glycine, taurine, and alpha-methyl glucoside by isolated renal tubules in vitro was studied in adult male rats. Parenteral administration of 400 mumol twice a day for four days of cystine dimethylester led to an increased urine volume, and excretion of phosphate, glucose, alpha-amino nitrogen, and the amino acids glutamine, proline, alanine, 1/2 cystine, ornithine, lysine, histidine, and glycine. Cystine dimethylester treatment did not affect the creatine clearance nor were any renal anatomic abnormalities noted. Intracellular cysteine, but not cystine, was increased in the kidney after the four days of treatment. Pre-incubation of isolated renal tubules with 2 mmol/L cystine dimethylester for ten minutes markedly inhibited the uptake of 0.025 mmol/L lysine, 0.1 mmol/L glycine, 0.01 mmol/L taurine, and 2 mmol/L alpha-methyl glucoside. Incubation with 2 mmol/L cystine dimethylester for ten minutes did not affect the ability of the renal tubule to exclude trypan blue dye, although longer incubation times did lead to significant staining. The intracellular cystine concentration of the renal tubule did rise significantly after incubation with cystine dimethylester, a biochemical correlate of the human disease cystinosis. These studies indicate that cystine dimethylester can induce an experimental form of the Fanconi syndrome both in vivo and in vitro and offers a new model for investigating the mechanisms underlying this enigmatic disorder.

Amino Acids↗

Cysteine and glutathione levels in developing rat kidney and liver.

Intracellular levels of cysteine (CSH) and reduced glutathione (GSH) in the kidney and liver of rats from the newborn to the adult period have been determined using a sensitive high performance liquid chromatography method. In the kidney, the intracellular level of free CSH increased 4-fold from 1 to 4 nmol/mg protein with GSH levels which ranged from 20 to 25 nmol/mg protein from the 10th to 21st postnatal day, respectively. In contrast, intracellular free hepatic CSH showed a biphasic pattern with development. Intracellular free hepatic GSH, on the other hand, increased 2-fold over the 3- to 21-day postnatal period. In adult tissues, intracellular levels of free CSH and GSH decreased as compared with levels in 21-day postnatal animals. When ratios of CSH to GSH were compared between tissues from the 3-day-old postnatal and adult rat, CSH:GSH increased approximately 4-fold in the kidney and decreased 2- to 3-fold in the liver.

Animals↗

Characteristics of lysine uptake by isolated renal cortical tubule fragments from mature and immature dogs.

The uptake of L-lysine was examined in isolated renal cortical tubule fragments from adult and 1-week-old dogs. Lysine uptake by adult tubules was initially more rapid than that by the immature tubules. This uptake by mature tubules reached a steady state after 30 min of incubation, while the newborn tubules still had not reached a steady state by 90 min of incubation. Because a steady state of lysine uptake was not attained with the immature tubules, their uptake of lysine exceeded that of the adult after 60 min of incubation. Kinetic studies revealed that lysine was taken up by one saturable transport system with a Km of 0.56 mM and Vmax of 6.18 mmol/liter intercellular fluid per 5 min in the adult and one saturable transport system in the 1-week-old with a Km of 0.38 mM and Vmax of 3.66 mmol/l intracellular fluid per 5 min. Lysine also entered the renal tubule cells in both age groups via a diffusional pathway with a kd of 0.35 min-1 in the adult and 0.30 min-1 in the newborn. Cystine competitively inhibited lysine uptake by adult dog tubules with a Ki of 0.61 mM. The other dibasic amino acids, ornithine and arginine, also inhibited lysine uptake in both the adult and the newborn.

Age Factors↗

Cystine-glutamate transport interactions in rat renal cortical tubules, brushborder vesicles, and cultured renal tubule cells.

Glutamate had no significant effect on the uptake of 0.025 mM cystine by isolated rat renal cortical tubules and brushborder membrane vesicles in contrast to lysine which significantly inhibits cystine transport. Glutamate, however, markedly inhibited cystine uptake by rat renal tubule cells grown in a serum-free, hormonally defined media for 5 days. Lysine also inhibited cystine transport in these cultured renal tubule cells.

Animals↗

Developmental aspects of cystine transport in the dog.

Developmental changes in cystine transport by the canine kidney were examined both in vivo and in vitro. Renal clearance studies indicated that cystine was one of the more incompletely reabsorbed amino acids at birth, but its reabsorption approaches adult levels by 21 days. Concomitantly, cystine uptake by isolated renal cortical tubule fragments from immature dogs was slower than that by renal tubules from adult dogs. Both age groups rapidly metabolized the transported cystine. This metabolism was principally to cysteine, but also small amounts of reduced glutathione were formed from the transported cystine. Concentration dependence studies indicated two transport systems for cystine uptake in both the immature and the adult dog. Both transport systems in the 1-wk-old dog had a somewhat greater affinity for cystine than the corresponding system in the adult, but this was offset by the markedly lower maximal transport rates for these systems in the 1-wk-old dog. The high affinity system was inhibited by lysine in tubules from both age groups. In the dog, the rise in the tubular reabsorption of cystine with maturation could, in part, be explained by an increase in the number of transport sites for cystine.

Animals↗

Uptake of proline by brushborder vesicles isolated from human kidney cortex.

Proline transport into renal brushborder membrane vesicles isolated from human kidney is mediated by two uptake systems. The high-affinity system is stimulated by a Na gradient and appears to be shared with glycine while the low-affinity system is not. Uptake curves of low concentrations of proline exhibit a Na-gradient-dependent overshoot indicative of electrogenic transport. The proline transport systems observed in isolated human renal brushborder membrane vesicles appear to have characteristics similar to those in rat kidney membranes.

Alanine↗

Absence of a role of gamma-glutamyl transpeptidase in the transport of amino acids by rat renal brushborder membrane vesicles.

The role of the enzyme, gamma-glutamyl transpeptidase on the uptake of amino acids by the brushborder membrane of the rat proximal tubule was examined by inhibiting it with AT-125 (L-[alpha S, 5S]-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid). AT-125 inhibited 98% of the activity of gamma-glutamyl transpeptidase when incubated for 20 min at 37 degrees C with rat brushborder membrane vesicles. AT-125 given to rats in vivo inhibited 90% of the activity of gamma-glutamyl transpeptidase in subsequently isolated brushborder membrane vesicles from these animals. AT-125 inhibition of gamma-glutamyl transpeptidase both in vivo and in vitro had no effect on the brushborder membrane uptake of cystine. Similarly, there was no effect of gamma-glutamyl transpeptidase inhibition by AT-125 on glutamine, proline, glycine, methionine, leucine or lysine uptake by brushborder membrane vesicles. Furthermore, the uptake of cystine by isolated rat renal cortical tubule fragments, in which the complete gamma-glutamyl cycle is present, was unaffected by AT-125 inhibition of gamma-glutamyl transpeptidase. Therefore, in the two model systems studied, gamma-glutamyl transpeptidase did not appear to play a role in the transport of amino acids by the renal brushborder membrane.

Amino Acids↗

Developmental aspects of sugar transport by isolated dog renal cortical tubules.

alpha-Methyl-D-glucoside (AMG) uptake was examined in isolated renal cortical tubules from newborn, 3-month-old, and adult dogs. All three age groups demonstrated active sugar transport. The initial rate of AMG uptake was similar in the 3-month-old and adult tubules which was twice that of the newborn. At steady-state, the adult and newborn tubules had achieved a similar intracellular AMG concentration which was 45% greater than that of the 3-month-old. Determination of the flux constants of these uptake patterns revealed that there was an age-dependent increase in both the net flux and the fractional influx rate constant. However, the 3-month-old had the highest fractional efflux rate constant and the newborn the lowest value with the adult in between. Kinetic analysis of AMG uptake showed a single saturable transport system for each age group. The newborn and adult had similar Km values but the 3-month-old had a value that was 60% higher. The 3-month-old tubules had the highest Vmax and the newborn tubules the lowest with the adult value in between. AMG uptake by tubules from each age group demonstrated a similar pattern of inhibition in a low sodium buffer and by glucose and phlorizin. This indicated that, aside from kinetic changes with maturation, the saturable transport system for AMG is similar in each age group.

Aging↗